Case Report: The effect of intravenous and oral antibiotics on the gut microbiome and breath volatile organic compounds over one year.

BACKGROUND: Antimicrobial resistance (AMR) is a global concern and better understanding of the gut microbiome, a known 'amplifier' of AMR, may allow future clinicians to tailor therapy to minimise this risk and offer a personalised medicine approach. To examine the gut microbiome, patients are required to provide faecal samples; more convenient and cheaper solutions need to be found. METHODS: As part of a pilot study looking at how routes of administration affect the gut microbiome in NHS patients undergoing routine clinical management for infections, we hypothesised that effects on the gut microbiome varied with the route and metabolism of antibiotic used, and these changes may be reflected in breath metabolites. We present a case report of a patient with an unusual clinical history, alongside breath metabolite and gut microbiome data taken before, during and after antibiotic therapy over a period of one year. RESULTS: We noted a shift in the dominant Bacteroides strain in the patient's gut microbiome between pre- and post-therapy samples, along with an alteration in the composition of breath metabolites. CONCLUSIONS: This study provides a framework for similar future work and highlights the need for further research on the relationships between changes in microbial gut communities and antimicrobial exposure, patient clinical status, and the metabolites of human breath.

Rare and unusual case of hepatic and disseminated tuberculosis in an immunocompetent patient.

Mycobacterium tuberculosis complex disease (tuberculosis (TB)) of the liver is rare and liver abscesses as a result are even rarer. In an immunocompetent individual, the disease tends to be localised. To the best of our knowledge, we report one of the most severe TB involvements of the liver in an immunocompetent individual. A young woman with a history of previous TB infection, presented in septic shock. Scans showed a liver filled with possible abscesses, one of which was aspirated and confirmed TB. Multiple HIV tests were negative but she remained lymphopaenic. Although she improved substantially with anti-tuberculous treatment, she later developed non-tuberculous central nervous system disease that we were unable to fully explain. Despite a stormy recovery period, she continues to do well.

Rare cutaneous myiasis of the face due to Lund's fly (Cordylobia rodhaini) in a British traveller returning from Uganda.

We present a rare cause for cutaneous furuncular myiasis in a 55-year-old British traveller returning from Uganda. Initially presenting with what appeared to be a cellulitic furuncle on her forehead, she returned to the emergency department 3 days later with extensive preseptal periorbital swelling and pain. Occlusive treatment with petroleum jelly was applied and one larva manually extracted and sent to London School of Tropical Medicine for examination. It was identified as Lund's Fly (Cordylobia rodhaini), a rare species from the rainforests of Africa with only one other case reported in the UK since 2015. Ultrasound imaging identified another larva, necessitating surgical exploration and cleaning. The lesion subsequently healed completely and the patient remains well.

Rethinking antimicrobial stewardship paradigms in the context of the gut microbiome.

Ongoing concerns over the presence and persistence of antimicrobial resistance (AMR), particularly in Gram-negative bacteria, continue to have significant global health impacts. The gastrointestinal tract, or 'gut', environment amplifies AMR in the human gut microbiome, even in the absence of antibiotics. It constitutes a complex and diverse community of organisms, and patterns and alterations within it are increasingly being found to be associated with states of health and disease. Our understanding of the effects of routes of administration of antimicrobials on the gut microbiome is still lacking despite recent advances in metagenomics. In this article we review current evidence for antibiotic effects on gut microbiota and explore possible prescribing and stewardship approaches that would seek to minimize these effects. If we are to preserve existing and new antimicrobials, we need to consider their use in the context of their effect on gut ecology, and the human microbiome in general.

Positron emission tomography and reframing vasculitis as a spectrum of disease when investigating a patient with a fever of unknown origin.

A retired businessman presented to the infectious diseases department with a history of ongoing fevers and myalgia and raised inflammatory markers. This continued despite adequate antibiotic treatment of an epididymo-orchitis. Extensive investigations, including bone marrow and liver biopsies and a positron emission tomography, did not reveal a cause but showed reactive change in the bone marrow. Later, he developed a vasculitic rash and vision loss due to non-arteritic anterior ischaemic optic neuropathy. High-dose steroids were immediately initiated. A temporal artery biopsy was performed, which confirmed a healing large vessel vasculitis, possibly giant cell arteritis. He has responded very well to therapy. We must better appreciate the limitations of positron emission tomography in investigating a fever of unknown origin. The case also encourages awareness of autoimmune disorders as the leading category of causative diseases for this in older age groups.

Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.

PURPOSE: Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response. EXPERIMENTAL DESIGN: Healthy participants with Fitzpatric skin type II or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea polyphenol treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products. There was a >60% increase in the area under the plasma EGCG concentration-time curve after 4 weeks of green tea polyphenol treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of EGCG after repeated green tea polyphenol treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of epigallocatechin and epicatechin were not affected by repeated green tea polyphenol treatment. Four weeks of green tea polyphenol treatment at the selected dose and dosing schedule did not provide protection against UV-induced erythema. CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily).